Bacterial infections after severe trauma represent a major health problem. the trauma patient has a greatly increased risk of developing bacterial septicemia because he has undergone adverse alterations in both his specific immune and non-specific inflammatory host resistance systems. This proposal's objective is to delineate those alterations in human mononuclear cell interactions which are associated with the specific immune system dsyfunctions occurring after injury. Our hypothesis is that severe injury triggers changes in crucial monocyte (M0) activities which are then reflected in inimical alterations in both the specific immune and non-specific inflammatory host defense systems. To characterize what sequence of events are proceeding towards loss of host defenses after severe injury, several preliminary goals must be achieved. First, we must identify which critical interactive inflammatory-immune pathways are altered after trauma. Second, we need to design assays which monitor critical M0 function. Third, to reduce the number of different assays required to profile the various inflammatory and immune M0 functions. Finally, the development of aberrant M0 functions should be correlated with the appearance of immune regulatory dysfunctions. We are initiating assays to monitor changes in the following M0 functions of major trauma patients: synthesis of complement components, production of prostaglandin E2, production of endogneous pyrogens, generation of tissue procoagulant factor, production of plasminogen activator and production of lysozyme. We will correlate any altered M0 activities detected in the trauma patients to aberrations in their immune functions as measured by a decrease in induction of immune antibody forming cells (AFC), an increase in generation of activity of suppressor T lymphocytes, an increase in inhibitory M0 or any other change in immune regulatory function. Determination of which regulatory dysfunction (M0 or T suppressor) appears initially after injury is important for the discernment of the underlying mechanisms which cause loss of host resistance. The development of assays to measure cricial M0 functions will not only benefit the monitoring of trauma patients' immune capacity but also will facilitate development of innovative therapy designed to prevent or attenuate the development of adverse post-trauma changes in these host defense systems.